Long telomeres: A new prognostic factor for severity in triple-negative breast cancer patients

Abstract

Telomeres play an important role in various cancer types, where gradual telomere shortening associated with mitotic division leads to cell senescence and apoptosis in early steps of transformation [1]. Abnormal telomere length (TL) may have prognostic significance of malignancy and cancer risk. There is growing evidence from cancer susceptibility and population studies that points to a correlation between genetic variants that shorten TL and an increased risk of cancer [2]. By contrast, reduced telomere shortening induced by mutations in the POT1 gene, encoding a member of the shelterin complex involved in telomere maintenance, lead to long telomeres and tumour progression in several cancer types such as chronic lymphocytic leukaemia, colorectal cancer, melanoma, glioma and angiosarcoma [3]. In breast cancer, TL has been frequently evaluated but previous studies did not establish robust prognostic and/or predictive correlations between TL and any of the three main molecular subtypes [4]. Previously, short but not long telomeres were suggested to be associated with more aggressive breast cancer subtypes [5]. TL does not seem to be associated with increased breast cancer risk either [6,7]. Lack of significant evidence can be explained by the recent observation that chemotherapy affects TL [8]. Thus, treatment-naïve patients should be considered in the studies that aim to correlate TL with disease susceptibility or clinical course, since chemotherapy-modified TL can bias the true biological associations.